UH3 Project: Pragmatic Trial of Higher vs. Lower Serum Phosphate Targets in Patients Undergoing Hemodialysis (HiLo)
Principal Investigator: Myles Wolf, MD, MMSc
Sponsoring Institution: Duke University
- DaVita, Inc.
- Dialysis Program, University of Utah Health
NIH Institute Providing Oversight: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Program Official: Susan Mendley (NIDDK)
Project Scientist: Kevin Chan (NIDDK)
ClinicalTrials.gov Identifier: NCT04095039
Trial Status: Not yet recruiting
The prevalence of end-stage renal disease (ESRD) continues to increase. Kidney transplantation is the preferred treatment for ESRD, but an insufficient organ supply renders dialysis the only viable treatment option for most patients with ESRD. Although clinical outcomes among patients receiving dialysis have improved modestly in recent years, annual rates of hospitalizations and mortality remain unacceptably high, and quality of life is poor. Poor outcomes are driven primarily by increased risk of cardiovascular disease (CVD), but interventions that are proven to improve outcomes in the general population by targeting traditional CVD risk factors have mostly failed in patients with ESRD. In response, the nephrology community has embraced targeting of kidney-specific risk factors, including hyperphosphatemia, in an effort to improve clinical outcomes. Current clinical practice guidelines advocate aggressive treatment of hyperphosphatemia to near normal levels using dietary phosphate binders and restrictive diets. The benefits of this approach, however, are unproven, and the optimal serum phosphate target remains unknown and potential harms of aggressive treatment have not been definitively identified.
The HiLo Demonstration Project plans to address these clinically important questions in a large, pragmatic, cluster-randomized trial that will compare the effects of liberalizing the serum phosphate target (“Hi”) versus maintaining aggressive phosphate control (“Lo”) for patients receiving treatment with maintenance hemodialysis. HiLo will be embedded in the clinical care delivery of 2 U.S. dialysis provider organizations. Pragmatic aspects of HiLo include using an electronic approach to obtain patient-level consent, testing the intervention under real-world conditions, and providing a precedent for a non-mortality primary endpoint in ESRD trials.